TABLE A9.
Summary of Potential Resistance Mechanisms in ctDNA Samples Collected At the End of Treatment
| Resistance Mechanism | Lorlatinib (n = 31) | Crizotinib (n = 90) | ||
|---|---|---|---|---|
| Baseline | End of Treatment | Baseline | End of Treatment | |
| Patients with reported results, No. (%) | 29 (94) | 31 (100) | 87 (97) | 89 (99) |
| Positive status, No. (%) | ||||
| ALK fusion | 15 (48) | 6 (19) | 47 (52) | 30 (33) |
| ALK mutation | 1 (3) | 1 (3) | 5 (6) | 11 (12) |
| TP53 mutation | 15 (48) | 16 (52) | 27 (30) | 23 (26) |
| MAPK pathway aberration | 0 | 3 (10) | 4 (4) | 4 (4) |
| PI3K/MTOR/PTEN pathway aberration | 1 (3) | 3 (10) | 1 (1) | 0 |
| RTK pathway aberration | 1 (3) | 6 (19) | 3 (3) | 5 (6) |
| Cell cycle pathway aberration | 4 (13) | 5 (16) | 4 (4) | 5 (6) |
| Other mutation | 12 (39) | 14 (45) | 36 (40) | 28 (31) |
| No ctDNA detected | 5 (16) | 8 (26) | 17 (19) | 29 (32) |
NOTE. Four patients were excluded from baseline because of missing sample or results not reported but were included in EOT as results were available. One patient was excluded from baseline and EOT because of results not reported. A patient could be classified in multiple categories. The following aberrations were identified: MAPK pathway aberration: BRAF V600E; V600Dup; R389C; G466E; or amplification; KRAS G12D; G12C; G12S; K117N; A146T; or amplification; NRAS G12D; or amplification. PI3K/MTOR/PTEN pathway aberration: PIK3CA E545K; E542K; K111E; R93Q; N1044K; or amplification; MTOR C1483F; PTEN Q214*. RTK pathway aberration: EGFR L858R; R1068Q; or amplification; ERBB2 A440T; R678Q; or amplification; KIT; MET; FGFR1; FGFR2; FGFR3; PDGFRA amplification; NCOA4-RET fusion. Cell cycle pathway aberration: CDK4; CDK6; CCND1; CCND2; CCNE1; or MYC amplification; CDKN2A E69* or Y44fs; RB1 M695fs; or K80*. Other gene aberration: Any alteration in any of the other genes included in the G360 panel (eg, APC, AR, ARID1A, ATM, etc).
Abbreviations: ctDNA, circulating tumor DNA; EOT, end of treatment.